Marrale Maurizio, Albanese Nadia Ninfa, Calì Francesco, Romano Valentino
Dipartimento di Fisica e Chimica, Università di Palermo, Palermo, Italy.
U.O.C. di Genetica Medica Laboratorio di Genetica Molecolare, Associazione Oasi Maria SS. (I.R.C.C.S.), Troina, Italy.
PLoS One. 2014 Mar 25;9(3):e90947. doi: 10.1371/journal.pone.0090947. eCollection 2014.
Autism Spectrum Disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies have investigated the role of de novo Copy Number Variants (CNVs) and microRNAs as important but distinct etiological factors in ASD. We developed a novel computational procedure to assess the potential pathogenic role of microRNA genes overlapping de novo CNVs in ASD patients. Here we show that for chromosomes # 1, 2 and 22 the actual number of miRNA loci affected by de novo CNVs in patients was found significantly higher than that estimated by Monte Carlo simulation of random CNV events. Out of 24 miRNA genes over-represented in CNVs from these three chromosomes only hsa-mir-4436b-1 and hsa-mir-4436b-2 have not been detected in CNVs from non-autistic subjects as reported in the Database of Genomic Variants. Altogether the results reported in this study represent a first step towards a full understanding of how a dysregulated expression of the 24 miRNAs genes affect neurodevelopment in autism. We also propose that the procedure used in this study can be effectively applied to CNVs/miRNA genes association data in other genomic disorders beyond autism.
自闭症谱系障碍（ASD）是具有复杂遗传起源的儿童神经发育障碍。先前的研究已调查了新生拷贝数变异（CNV）和微小RNA作为ASD中重要但不同的病因学因素所起的作用。我们开发了一种新颖的计算程序，以评估与新生CNV重叠的微小RNA基因在ASD患者中的潜在致病作用。在此我们表明，对于1号、2号和22号染色体，患者中受新生CNV影响的miRNA基因座实际数量显著高于通过随机CNV事件的蒙特卡洛模拟估计的数量。在这三条染色体的CNV中过度表达的24个miRNA基因中，只有hsa-mir-4436b-1和hsa-mir-4436b-2在基因组变异数据库中未在非自闭症受试者的CNV中被检测到。本研究报告的结果总体上代表了朝着全面理解这24个miRNA基因的表达失调如何影响自闭症神经发育迈出的第一步。我们还提出，本研究中使用的程序可以有效地应用于自闭症以外的其他基因组疾病中的CNV/miRNA基因关联数据。
